U.S. Pat. No. 5,489,425 (Dow Chemical) discloses a range of open-chain and macrocyclic functionalised tetra-amine chelators useful for the complexation of metals, in particular radioactive and non-radioactive rhodium complexes, especially 105Rh or 101mRh radiometal complexes. Specific tetramines disclosed include:
 [Linker]Compound—CH2[p-phenylene]-BA-2,3,2-tet-[p-phenylene]-AN-2,3,2-tet—(CH2)3—PA-2,3,2-tet
The bifunctional chelators are described as useful for conjugation with monoclonal antibodies, or fragments thereof, for therapeutic or diagnostic purposes. U.S. Pat. No. 5,489,425 discloses (Examples 21, 22a and 23) that the antibody-radiometal complex chelator conjugate is prepared by first forming the 105Rh metal complex, then reaction with the antibody followed by purification. U.S. Pat. No. 5,489,425 is silent on antibody-chelator conjugates which are uncomplexed, ie. without a coordinated radiometal. U.S. Pat. No. 5,489,425 does not teach how to differentiate the pendant amine from the four amines of the chelator in such antibody conjugation reactions. U.S. Pat. No. 5,489,425 states that the bifunctional chelators “would also be useful in complexing technetium and rhenium”, but does not disclose how this would be achieved or any actual technetium complexes.
U.S. Pat. No. 5,650,134 discloses somatostatin peptide-chelator conjugate of a range of chelators. Example 1 describes the conjugation to a 6-(p-isothiocyanatobenzyl)-1,4,8,11-tetraazaundecane to an octreotide peptide.
EP 1181936 A1 discloses bombesin (ie. tetradecapeptide) conjugates of tetra-amine chelators, prepared using the bifunctional chelators BBN-1 and BBN-2, and the 99mTc complexes thereof:

The 99mTc complexes are said to exhibit rapid clearance from the murine body via the kidneys and urinary system. EP 1181936 A1 does not, however, provide any disclosure or reference to the synthesis of BBN-1 or BBN-2, only to the step where they are conjugated to the N-terminus of bombesin. The conjugation of BBN-2 to bombesin and 99mTc labelling to give a potential tumour imaging radiopharmaceutical has also been described by Nock et al [Eur. J. Nucl. Med., 30(2), 247-258 (2003)]. The 99mTc complex is said to impart improved hydrophilicity compared to prior art bombesin-chelate conjugates, and hence be expected to favour excretion via the kidneys and urinary system.
The conjugation of BBN-1 to octreotide and 99mTc labelling to give a potential tumour imaging radiopharmaceutical has been described by Maina et al for human patients [Eur. J. Nucl. Med., 30(9), 1211-1219 (2003)]. Neither of the above BBN-1 or BBN-2 publications provide any synthesis of BBN-1 or BBN-2.